CN111084760A - Preparation process of potassium dehydroandrographolide succinate for injection - Google Patents
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Abstract
The invention provides a preparation process of potassium dehydroandrographolide succinate for injection, which comprises the following steps: A) adjusting the pH of the citric acid aqueous solution to 7.0-7.5 by using a pH regulator to obtain a mixed solution; B) mixing and stirring part of water for injection and potassium dehydroandrographolide succinate according to the prescription amount, adding sodium bicarbonate and cysteine hydrochloride, heating and stirring at the temperature of 60-75 ℃, adding the mixed solution, and adjusting the pH to 7.0-7.5 by using a pH regulator to obtain a precursor solution; C) sequentially carrying out activated carbon adsorption, decarburization and constant volume on the precursor solution to obtain a raw material solution; D) and (3) freeze-drying the raw material liquid to obtain the potassium dehydroandrographolide succinate powder injection for injection. The invention adopts the method of controlling the temperature and pH value of the water for injection, adding a proper amount of antioxidant and keeping the temperature to prepare the dehydroandrographolide succinate freeze-dried powder injection, and has the outstanding characteristics of strong operability, lower production cost, strong stability, less impurities, safe and reliable quality and the like.
Description
Technical Field
The invention belongs to the technical field of medicines, and particularly relates to a preparation process of potassium dehydroandrographolide succinate for injection.
Background
The andrographolide for injection is prepared with andrographolide as one kind of acanthaceae plant, and through esterification, dewatering and salification, and is prepared into 14-decarboxylation-11, 12-didehydro andrographolide-3, 19-potassium hemisuccinate monopotassium salt, adding pH regulator, sodium bicarbonate and other supplementary material and freeze drying to prepare the aseptic powder for intramuscular injection. Potassium dehydroandrographolide succinate for injection is antiviral drug, contains potassium dehydroandrographolide succinate as main ingredient, and can be used for treating viral pneumonia and viral upper respiratory infection. The product has antiinflammatory, antipyretic, tranquilizing, and antiviral effects, and can be used for inactivating influenza virus, enterosyncytial virus, pneumonia adenovirus, and respiratory syncytial virus. The adverse reactions are reported to be skin anaphylaxis, infantile diarrhea, occasional anaphylactic shock, liver function damage and the like. This herb should not be combined with acidic or alkaline drugs or sodium bisulfite.
In 2018, the national food and drug administration revises the relevant regulations of the national drug standard of potassium dehydroandrographolide succinate for injection on the content of impurities, and changes the content standard of the impurities from single impurity less than 2 percent and total impurity less than 4 percent into single impurity 1 percent and total impurity less than 2 percent. The requirement of potassium dehydroandrographolide succinate for injection on impurities is more strict, and when the content of the impurities is too high, the side effect is increased, the irritation is enhanced, and the color is yellow. The existing patent standard is the impurity content standard of the injection which is provided by the state, and the impurity content of the injection does not meet the current market demand or even the national standard. A new preparation method of the dehydroandrographolide succinate freeze-dried powder for injection is needed at present, and the dehydroandrographolide succinate for injection with less impurities and higher quality standard is produced to meet the quality requirement of the market on the dehydroandrographolide succinate for injection.
Although the prior art in China can produce the potassium dehydroandrographolide succinate for injection, the prior art has a series of defects of high impurity content, complex process, more control variables, high production cost and the like.
Chinese patent CN 103040767A discloses a stable potassium dehydroandrographolide succinate freeze-dried powder injection, which provides a potassium dehydroandrographolide succinate freeze-dried powder injection, which comprises potassium dehydroandrographolide succinate, alkali metal salt and optional pharmaceutically acceptable auxiliary materials, and the potassium dehydroandrographolide succinate freeze-dried powder injection is prepared. Dissolving alkali metal salt in appropriate amount of water for injection, adding potassium dehydroandrographolide succinate, and stirring to dissolve. Secondly, adding optional pharmaceutically acceptable auxiliary materials into the solution for dissolving, adding a proper amount of water to ensure that the concentration of solute in the solution reaches 5% -20%, filtering and sterilizing by using a 0.22 mu m microporous filter membrane, subpackaging the liquid medicine into penicillin bottles, transferring the liquid medicine into a freeze dryer, freeze-drying the liquid medicine, pressing and sealing to obtain the penicillin. The patent teaches a preparation method of potassium dehydroandrographolide succinate, but potassium dehydroandrographolide succinate for injection prepared according to the operation steps has high impurity content and yellow color, and the impurity content cannot meet the new standard requirements of national pharmacopoeia.
Chinese patent CN 108836945A discloses a 'preparation method of a dehydroandrographolide succinate freeze-dried powder injection for injection', which belongs to the field of pharmacy and mainly comprises the steps of material preparation, medicine preparation, filtration, storage, pre-freezing, drying and the like, and finally the finished product of the dehydroandrographolide succinate freeze-dried powder injection for injection is obtained. The filtering step comprises the steps of adding a preset amount of activated carbon into the liquid medicine A, uniformly stirring, decarburizing and roughly filtering by using a filter element, finely filtering by using a filter membrane, and performing at least two procedures, wherein the drying step comprises the step of heating the partition plate twice respectively. The preparation method of the potassium dehydroandrographolide succinate freeze-dried powder injection for injection is provided. The potassium dehydroandrographolide succinate for injection prepared by the patent has the problems of too high content, yellow color and the like.
Although the current domestic applied patent can only adapt to the previous impurity content standard, the single impurity content is not more than 2 percent, the total impurity content is not more than 4 percent, and the standard of 2018 countries on impurities, the single impurity content is not more than 1 percent, and the total impurity content is not more than 2 percent, can not be met. The produced product has too many impurities, and also has the defects of long production period, many control variables, complex process, more energy consumption, overhigh cost and the like.
Disclosure of Invention
In view of the above, the technical problem to be solved by the invention is to provide a preparation process of potassium dehydroandrographolide succinate for injection, the preparation process provided by the invention has strong operability and lower production cost, and the obtained potassium dehydroandrographolide succinate powder injection for injection has strong stability, less impurities and safe and reliable quality.
The invention provides a preparation process of potassium dehydroandrographolide succinate for injection, which comprises the following steps:
A) adjusting the pH of the citric acid aqueous solution to 7.0-7.5 by using a pH regulator to obtain a mixed solution;
B) mixing and stirring part of water for injection and potassium dehydroandrographolide succinate according to the prescription amount, adding sodium bicarbonate and cysteine hydrochloride, heating and stirring at the temperature of 60-75 ℃, adding the mixed solution, and adjusting the pH to 7.0-7.5 by using a pH regulator to obtain a precursor solution;
C) sequentially carrying out activated carbon adsorption, decarburization and constant volume on the precursor solution to obtain a raw material solution;
D) and (3) freeze-drying the raw material liquid to obtain the potassium dehydroandrographolide succinate powder injection for injection.
Preferably, in the step A), the pH regulator is arginine, and the concentration of the pH regulator is 5 wt% to 15 wt%.
Preferably, the amount of the part of the water for injection is 50 to 70 percent of the total volume of the raw material liquid.
Preferably, in the step B), an arginine aqueous solution is used for adjusting the pH value, and the concentration of the arginine aqueous solution is 5-15 wt%.
Preferably, the mass-volume ratio of the added amount of the activated carbon to the precursor solution is (0.05-0.2) g: 100 ml.
Preferably, the adsorption time of the activated carbon is 10-20 min.
Preferably, the freeze-drying method comprises the following steps:
and (3) sequentially pre-freezing, sublimating, drying, analyzing and drying the raw material solution to obtain the potassium dehydroandrographolide succinate powder injection for injection.
Preferably, the freeze-drying method comprises the following steps:
pre-freezing the raw material liquid for 0.5-3 h at the temperature of-40 to-35 ℃ to obtain a pre-frozen raw material;
heating the pre-frozen raw material to-6-0 ℃ at a heating rate of 3-7 ℃ for 5-10 hours;
and then heating to 40-45 ℃ at the heating rate of 4-6 ℃, and preserving the heat for 2-5 hours to obtain the potassium dehydroandrographolide succinate powder injection for injection.
Preferably, the vacuum degree of the freeze drying is less than or equal to 0.15 mbar.
Preferably, the mass ratio of the potassium dehydroandrographolide succinate to the sodium bicarbonate to the cysteine hydrochloride to the citric acid is 100: (14-18): (0.2-2): (2-6).
Compared with the prior art, the invention provides a preparation process of potassium dehydroandrographolide succinate for injection, which comprises the following steps: A) adjusting the pH of the citric acid aqueous solution to 7.0-7.5 by using a pH regulator aqueous solution to obtain a mixed solution; B) mixing and stirring part of water for injection and potassium dehydroandrographolide succinate according to the prescription amount, adding sodium bicarbonate and cysteine hydrochloride, heating and stirring at the temperature of 60-75 ℃, adding the mixed solution, and adjusting the pH value to 7.0-7.5 to obtain a precursor solution; C) sequentially carrying out activated carbon adsorption, decarburization and constant volume on the precursor solution to obtain a raw material solution; D) and (3) freeze-drying the raw material liquid to obtain the potassium dehydroandrographolide succinate powder injection for injection. The invention adopts the method of controlling the temperature and pH value of the water for injection, adding a proper amount of antioxidant and keeping the temperature to prepare the dehydroandrographolide succinate freeze-dried powder injection, and has the outstanding characteristics of strong operability, lower production cost, strong stability, less impurities, safe and reliable quality and the like.
Detailed Description
The invention provides a preparation process of potassium dehydroandrographolide succinate for injection, which comprises the following steps:
A) adjusting the pH of the citric acid aqueous solution to 7.0-7.5 by using a pH regulator to obtain a mixed solution;
B) mixing and stirring part of water for injection and potassium dehydroandrographolide succinate according to the prescription amount, adding sodium bicarbonate and cysteine hydrochloride, heating and stirring at the temperature of 60-75 ℃, adding the mixed solution, and adjusting the pH value to 7.0-7.5 to obtain a precursor solution;
C) sequentially carrying out activated carbon adsorption, decarburization and constant volume on the precursor solution to obtain a raw material solution;
D) and (3) freeze-drying the raw material liquid to obtain the potassium dehydroandrographolide succinate powder injection for injection.
Firstly, adjusting the pH of citric acid to 7.0-7.5 by using an aqueous solution of a pH regulator to obtain a mixed solution. In the invention, the pH regulator is selected from arginine, and the concentration of the aqueous solution of the pH regulator is 5 wt% -15 wt%, preferably 7 wt% -12 wt%, and more preferably 10 wt%.
Mixing and stirring part of water for injection and potassium dehydroandrographolide succinate according to the prescription amount, adding sodium bicarbonate and cysteine hydrochloride, heating and stirring at the temperature of 60-75 ℃, wherein the amount of the part of water for injection is 50-70% of the total volume of the raw material liquid, and the preferable amount is 55-65%. The heating and stirring temperature is preferably 65-70 ℃.
And then adding the prepared mixed solution, and adjusting the pH value to 7.0-7.5 to obtain a precursor solution. Wherein, the pH value is adjusted by using an arginine aqueous solution, and the concentration of the arginine aqueous solution is 5 wt% -15 wt%, preferably 7 wt% -12 wt%, and more preferably 10 wt%.
Then sequentially carrying out activated carbon adsorption, decarburization and constant volume on the precursor solution to obtain a raw material solution
The mass volume ratio of the added amount of the activated carbon to the precursor solution is (0.05-0.2) g: 100ml, preferably (0.07 to 0.15) g: 100ml, more preferably 0.1 g: 100 ml. And when activated carbon adsorption is carried out, the precursor solution is preferably continuously stirred, and the activated carbon adsorption time is 10-20 min, preferably 12-18 min.
Next, decarburization is carried out, and the method of decarburization in the present invention is not particularly limited, and a decarburization method known to those skilled in the art may be used. In the present invention, the decarburization is preferably carried out by a filtration method.
Then, the filtrate obtained after the decarburization is subjected to constant volume, and in the present invention, the volume is determined by using water for injection.
In the invention, the raw material liquid comprises the following raw materials in proportion: the mass ratio of the potassium dehydroandrographolide succinate to the sodium bicarbonate to the cysteine hydrochloride to the citric acid is 100: (14-18): (0.2-2): (2-6).
In some embodiments of the present invention, the mass ratio of potassium dehydroandrographolide succinate, sodium bicarbonate, cysteine hydrochloride and citric acid is 100: 15: 1: 3.
wherein the specification of the potassium dehydroandrographolide succinate powder injection is 40mg, 100mg, 200mg or 400mg, and different amounts of raw material liquid can be prepared according to different specifications.
In some specific embodiments of the invention, the raw material formulas of the potassium dehydroandrographolide succinate powder injection for injection with different specifications are specifically shown in tables 1-4.
Table 1 specification 1: 200 mg/count
Table 2 specification 2: 400 mg/piece
Table 3, specification 3: 40 mg/count
Table 4 specification 4: 100 mg/count
Meanwhile, in the invention, when the raw material liquid is prepared, the pH value of the raw material liquid needs to be adjusted by using the water solution of the pH adjusting agent, and the adding amount of the pH adjusting agent is enough to keep the pH value of the raw material liquid at 7.0-7.5.
The prepared raw material liquid is stored at the temperature of 5-25 ℃ and is filled within 6 hours.
And finally, freeze-drying the raw material liquid to obtain the potassium dehydroandrographolide succinate powder injection for injection.
The freeze drying method comprises the following steps:
and (3) sequentially pre-freezing, sublimating, drying, analyzing and drying the raw material solution to obtain the potassium dehydroandrographolide succinate powder injection for injection.
Specifically, pre-freezing the raw material liquid for 0.5-3 h at-35 ℃ to obtain a pre-frozen raw material;
heating the pre-frozen raw material to-6-0 ℃ at a heating rate of 3-7 ℃ for 5-10 hours;
then heating to 40-45 ℃ at the heating rate of 4-6 ℃, and preserving heat for 2-5 hours to obtain the potassium dehydroandrographolide succinate powder injection for injection
In the invention, the vacuum degree of the freeze drying is less than or equal to 0.15 mbar.
The invention adopts the method of controlling the temperature and pH value of the water for injection, adding a proper amount of antioxidant and keeping the temperature to prepare the dehydroandrographolide succinate freeze-dried powder injection, and has the outstanding characteristics of strong operability, lower production cost, strong stability, less impurities, safe and reliable quality and the like.
For further understanding of the present invention, the following examples are provided to illustrate the preparation process of potassium dehydroandrographolide succinate for injection, and the scope of the present invention is not limited by the following examples.
Example 1
1. The raw material formulation (200 mg/count for example) is shown in Table 5
Table 5 raw material formulation table
2. The preparation method comprises the following steps:
① the citric acid is dissolved in water for injection, and the pH is adjusted to 7.0 with 10% arginine solution to obtain solution 1.
② adding water for injection 70% of the total volume in the concentrating tank, adding potassium dehydroandrographolide succinate, and stirring.
③ the prescribed amounts of sodium bicarbonate and cysteine hydrochloride were added, heated and stirred, maintaining the temperature at 65 ℃.
④ adding solution 1 into the concentration tank, detecting pH, adding 10% arginine solution, and adjusting pH to 7.5.
⑤ adding 0.1% (g/ml) active carbon according to the total volume, stirring for 10min, decarbonizing, and metering volume.
⑥ the storage temperature of the filtrate is controlled at 5 deg.C, and the filtrate is filled within 6 hr to obtain raw material solution.
Example 2
1. The formulation is the same as that of example 1
2. Preparation method
① the citric acid is dissolved in water for injection, and the pH is adjusted to 7.5 with 10% arginine solution to obtain solution 1.
② adding 60% water for injection into the concentrating tank, adding potassium dehydroandrographolide succinate, and stirring.
③ the prescribed amounts of sodium bicarbonate and cysteine hydrochloride were added, heated and stirred, maintaining the temperature at 60 ℃.
④ adding solution 1 into the concentration tank, detecting pH, adding 10% arginine solution, and adjusting pH to 7.0.
⑤ adding 0.1% (g/ml) active carbon according to the total volume, stirring for 20min, decarbonizing, and metering volume.
⑥ the storage temperature of the filtrate is controlled at 10 deg.C, and the filtrate is filled within 6 hr to obtain raw material liquid.
Example 3
1. The formulation is the same as that of example 1
2. Preparation method
① the citric acid is dissolved in water for injection, and the pH is adjusted to 7.2 with 10% arginine solution to obtain solution 1.
② adding water for injection 50% of the total volume, adding potassium dehydroandrographolide succinate, and stirring.
③ the prescribed amounts of sodium bicarbonate and cysteine hydrochloride were added, heated and stirred, maintaining the temperature at 75 ℃.
④ adding solution 1 into the concentration tank, detecting pH, adding 10% arginine solution, and adjusting pH to 7.2.
⑤ adding 0.1% (g/ml) active carbon according to the total volume, stirring for 20min, decarbonizing, and metering volume.
⑥ the storage temperature of the filtrate is controlled at 25 deg.C, and the filtrate is filled within 6 hr to obtain raw material liquid.
Example 4
1. The formulation is the same as that of example 1
2. Preparation method
① the citric acid is dissolved in water for injection, and the pH is adjusted to 7.0 with 10% arginine solution to obtain solution 1.
② adding water for injection 50% of the total volume, adding potassium dehydroandrographolide succinate, and stirring.
③ the prescribed amounts of sodium bicarbonate and cysteine hydrochloride were added, heated and stirred, maintaining the temperature at 75 ℃.
④ adding solution 1 into the concentration tank, detecting pH, adding 10% arginine solution, and adjusting pH to 7.5.
⑤ adding 0.1% (g/ml) active carbon according to the total volume, stirring for 10min, decarbonizing, and metering volume.
⑥ the storage temperature of the filtrate is controlled at 15 deg.C, and the filtrate is filled within 6 hr to obtain raw material liquid.
Example 5
1. The formulation is the same as that of example 1
2. Preparation method
① the citric acid is dissolved in water for injection, and the pH is adjusted to 7.5 with 10% arginine solution to obtain solution 1.
② adding water for injection 70% of the total volume in the concentrating tank, adding potassium dehydroandrographolide succinate, and stirring.
③ the prescribed amounts of sodium bicarbonate and cysteine hydrochloride were added, heated and stirred, maintaining the temperature at 60 ℃.
④ adding solution 1 into the concentration tank, detecting pH, adding 10% arginine solution, and adjusting pH to 7.0.
⑤ adding 0.1% (g/ml) active carbon according to the total volume, stirring for 15min, decarbonizing, and metering volume.
⑥ the storage temperature of the filtrate is controlled at 5 deg.C, and the filtrate is filled within 6 hr to obtain raw material solution.
Comparative example 1
1. The raw material formulation (200 mg/count for example) is shown in Table 6
Table 6 raw material formula table
2. The preparation method comprises the following steps:
① the water for injection is added to the tank in a concentration ratio of 60% of the total volume, and the sodium bicarbonate is added and stirred.
② weighing Chuanhuning, adding into a concentration tank, and stirring.
③ phosphoric acid was added in the prescribed amount, heated and stirred, and the temperature was maintained at 65 ℃.
④ the pH was measured and sodium dihydrogen phosphate was added to adjust the pH to 7.0.
⑤ filtering with 0.22 μm microporous membrane for sterilization, and diluting to desired volume to obtain raw material solution.
Comparative example 2
1. The formula of the raw materials and auxiliary materials (taking 80 mg/unit as an example) is shown in Table 7
TABLE 7 raw and auxiliary materials formula
2. The preparation method comprises the following steps:
① dispensing medicine, namely adding potassium dehydroandrographolide succinate and sodium bicarbonate into injection water with the total volume of 60%, stirring to completely dissolve, and adding the rest injection water to full volume to obtain liquid medicine A;
② filtering, adding activated carbon, decarbonizing, coarse filtering, fine filtering with filter membrane to obtain liquid B, and sampling and inspecting;
③, storing, namely conveying the qualified liquid medicine B to liquid medicine storage tanks of a filling room, and respectively filling the liquid medicine B into penicillin bottles for later use.
Example 6
Freeze-drying the raw material liquid obtained in the examples 1-5 and the comparative examples 1-2, wherein the specific freeze-drying process is as follows:
1. pre-freezing: reducing the temperature of the front box product to below-35 ℃; vacuumizing, keeping the vacuum degree within the range of less than or equal to 0.15mbar, and pre-freezing the raw material liquid in a freeze dryer for 2 hours;
2. sublimation: refrigerating the oil temperature of the vacuum freeze drying box to-4 ℃ at the speed of 3-7 ℃/h, and maintaining for 6 hours;
3. and (3) heat preservation: regulating the sublimation rate by regulating the vacuum degree in the drying box, controlling the temperature of the product at 40-45 ℃, and preserving the heat for 2-5 hours;
4. judging the end point, closing the septum valve, reaching the set time for 3min, finishing the self-running if the vacuum leakage is lower than the set value (<5Pa), alarming if the vacuum leakage is higher than the set value, and continuing the second-stage drying until the leakage is smaller than the set value;
5. and (5) tamponade and discharging from the box to obtain the potassium dehydroandrographolide succinate powder injection for injection.
Example 7
The performance of the potassium dehydroandrographolide succinate powder injection prepared in example 6 was measured, and the results are shown in Table 8
Long term stability studies were conducted on the products of the above examples and comparative examples. The results are shown in tables 9 to 15.
As can be seen from Table 8, the dehydroandrographolide succinate lyophilized powder for injection prepared by controlling the temperature and pH value of the water for injection, and combining the addition of an appropriate amount of antioxidant and the heat preservation temperature has the outstanding characteristics of good impurity control, stable content and the like. .
The foregoing is only a preferred embodiment of the present invention, and it should be noted that, for those skilled in the art, various modifications and decorations can be made without departing from the principle of the present invention, and these modifications and decorations should also be regarded as the protection scope of the present invention.
Claims (10)
1. The preparation process of the potassium dehydroandrographolide succinate for injection is characterized by comprising the following steps of:
A) adjusting the pH of the citric acid aqueous solution to 7.0-7.5 by using a pH regulator to obtain a mixed solution;
B) mixing and stirring part of water for injection and potassium dehydroandrographolide succinate according to the prescription amount, adding sodium bicarbonate and cysteine hydrochloride, heating and stirring at the temperature of 60-75 ℃, adding the mixed solution, and adjusting the pH to 7.0-7.5 by using a pH regulator to obtain a precursor solution;
C) sequentially carrying out activated carbon adsorption, decarburization and constant volume on the precursor solution to obtain a raw material solution;
D) and (3) freeze-drying the raw material liquid to obtain the potassium dehydroandrographolide succinate powder injection for injection.
2. The preparation process according to claim 1, wherein in the step A), the pH regulator is arginine, and the concentration of the pH regulator is 5-15 wt%.
3. The process according to claim 1, wherein the amount of the part of the water for injection is 50 to 70% of the total volume of the raw material solution.
4. The preparation process according to claim 1, wherein in the step B), the pH value is adjusted by using an arginine aqueous solution, and the concentration of the arginine aqueous solution is 5-15 wt%.
5. The preparation process according to claim 1, wherein the mass-to-volume ratio of the added amount of the activated carbon to the precursor solution is (0.05-0.2) g: 100 ml.
6. The preparation method according to claim 1, wherein the time for the activated carbon adsorption is 10-20 min.
7. The method of claim 1, wherein the freeze-drying is performed by:
and (3) sequentially pre-freezing, sublimating, drying, analyzing and drying the raw material solution to obtain the potassium dehydroandrographolide succinate powder injection for injection.
8. The method of claim 7, wherein the freeze-drying is performed by:
pre-freezing the raw material liquid for 0.5-3 h at the temperature of-40 to-35 ℃ to obtain a pre-frozen raw material;
heating the pre-frozen raw material to-6-0 ℃ at a heating rate of 3-7 ℃ for 5-10 hours;
and then heating to 40-45 ℃ at the heating rate of 4-6 ℃, and preserving the heat for 2-5 hours to obtain the potassium dehydroandrographolide succinate powder injection for injection.
9. The method according to claim 7, wherein the vacuum degree of the freeze-drying is 0.15mbar or less.
10. The preparation method according to claim 7, wherein the mass ratio of the potassium dehydroandrographolide succinate to the sodium bicarbonate to the cysteine hydrochloride to the citric acid is 100: (14-18): (0.2-2): (2-6).
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| US20130005722A1 (en) * | 2010-03-23 | 2013-01-03 | Manoj Senapati | Pharmaceutical Composition of Mycophenolate Mofetil and Process for Preparing Thereof |
| CN103040767A (en) * | 2013-01-11 | 2013-04-17 | 成都天台山制药有限公司 | Stable kalii dehydrographolidi succinas freeze-dried powder injection for injection |
| CN104414965A (en) * | 2013-08-20 | 2015-03-18 | 哈药集团三精制药股份有限公司 | Preparation method of kalil dehydrographolidi succinatis for injection |
| CN108836945A (en) * | 2018-09-12 | 2018-11-20 | 海南通用康力制药有限公司 | A kind of preparation method of Potassium DehydroandrograpolidSuccinate Succinate for Injection freeze drying powder injection |
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| US20130005722A1 (en) * | 2010-03-23 | 2013-01-03 | Manoj Senapati | Pharmaceutical Composition of Mycophenolate Mofetil and Process for Preparing Thereof |
| CN103040767A (en) * | 2013-01-11 | 2013-04-17 | 成都天台山制药有限公司 | Stable kalii dehydrographolidi succinas freeze-dried powder injection for injection |
| CN104414965A (en) * | 2013-08-20 | 2015-03-18 | 哈药集团三精制药股份有限公司 | Preparation method of kalil dehydrographolidi succinatis for injection |
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